Source: Health Products Regulatory Authority (IE) Revision Year: 2019 Publisher: Bayer Limited, The Atrium, Blackthorn Road, Dublin 18, Ireland
Urografin is not to be used for myelography, ventriculography or cisternography, since it is likely to provoke neurotoxic symptoms (pain, convulsions and coma, often with lethal outcome) in these examinations.
The use of contrast media should be carried out under the supervision of trained personnel whose experience qualifies them in the safe conduct of such examinations.
This medicinal product contains 362.50 mg of sodium in each dose (250 mL), equivalent to 18.1% of the WHO recommended maximum daily intake of 2 g sodium for an adult.
Occasionally, allergy-like hypersensitivity reactions have been observed after the use of X-ray contrast media such as Urografin (see 4.8, Undesirable effects). These reactions are usually manifest as non-serious respiratory or cutaneous symptoms, as mild respiratory distress, reddening of the skin (erythema), urticaria, itching or facial oedema. Serious events such as angioedema, subglottic oedema, bronchospasm and allergic shock are possible. Generally these reactions occur within one hour after administration of contrast media. However, in rare cases delayed reactions may occur (after hours to days).
Patients with hypersensitivity or a previous reaction to iodinated contrast media are at increased risk of having a severe reaction.
Before any contrast medium is injected, the patient should be questioned for a history of allergy (e.g. seafood allergy, hay fever, hives), sensitivity to iodine or to radiographic media and bronchial asthma as the reported incidence of adverse reactions to contrast media is higher in patients with these conditions and premedication with antihistamines and/or glucocorticoids may be considered.
Patients with bronchial asthma are at special risk of having bronchospasm or a hypersensitivity reaction.
Hypersensitivity reactions can be aggravated in patients on beta-blockers, particularly in the presence of bronchial asthma. Moreover, it should be considered that patients on beta-blockers may be refractory to standard treatment of hypersensitivity reactions with beta-agonists.
If hypersensitivity reactions occur (see 4.8, Undesirable effects), administration of the contrast medium must be discontinued immediately and – if necessary – specific therapy instituted via a venous access. It is therefore advisable to use a flexible indwelling cannula for intravenous contrast medium administration. To permit immediate countermeasures to be taken in emergencies, appropriate drugs, an endotracheal tube and a respirator should be ready at hand.
Particularly careful risk-benefit assessment is required in patients with known or suspected hyperthyroidism or goiter, as iodinated contrast media may interefere with thyroid function, aggravate or induce hyperthyroidism and thyreotoxic crisis.
Testing of thyroid function prior to Urografin administration and/or preventive thyreostatic medication may be considered in patients with known or suspected hyperthyroidism.
In neonates, specially preterm infants, who have been exposed to Urografin, either through the mother during pregnancy or in the neonatal period, it is recommended to monitor thyroid function, as exposure to excess iodine may cause hypothyroidism, possibly requiring treatment.
There is an increased risk of severe reactions in individuals with severe cardiac disease and particularly in those with heart failure and coronary artery disease.
Underlying vascular pathology and neurological disorders often seen in the elderly constitute an increased risk of adverse reactions to iodinated contrast media.
The need for examination merits particularly careful consideration in patients with a very poor general state of health.
Temporary renal failure may occur in rare cases. Preventive measures against acute renal failure following contrast medium administration include:
Identification of high-risk patients, e.g. patients with: a history of renal disease, pre-existing renal insufficiency, previous renal failure after contrast medium administration, diabetes mellitus with nephropathy, volume depletion, multiple myeloma, age greater than 60 years, advanced vascular disease, paraproteinemia, severe and chronic hypertension, gout, patients receiving large or repeated doses.
Ensuring adequate hydration in risk patients before contrast medium administration, preferably by maintaining intravascular infusion before and after the procedure and until the contrast medium has been cleared by the kidneys.
Avoiding additional strain on the kidneys in the form of nephrotoxic drugs, oral cholecystographic agents, arterial clamping, renal arterial angioplasty, major surgery etc. until the contrast medium has been cleared.
Postponing a new contrast medium examination until renal function returns to pre-examination levels.
Patients on dialysis may receive contrast media for radiological procedures as iodinated contrast media are cleared by the dialysis process.
The use of renally excreted intravascular X-ray contrast media can lead to transient impairment of kidney function. This may result in lactic acidosis in patients who are taking biguanides.
In patients with valvular disease and pulmonary hypertension contrast medium administration may lead to pronounced hemodynamic changes. Reactions involving ischaemic ECG changes and major arrhythmia are more common in older patients and in those with pre-existing cardiac disease.
The intravascular injection of contrast media may precipitate pulmonary oedema in patients with heart failure.
Particular care should be paid to the intravascular administration of contrast media in patients with acute cerebral infarction, acute intracranial haemorrhage, and other conditions involving blood-brain barrier damage, cerebral oedema or acute demyelination. Intracranial tumours or metastases and a history of epilepsy may increase the incidence of convulsive seizures after administration of iodinated contrast media. Neurological symptoms due to cerebrovascular disease, intracranial tumours or metastases, degenerative or inflammatory pathologies may be exacerbated by contrast medium administration. Vasospasm and subsequent cerebral ischaemic phenomena may be caused by intraarterial injections of contrast media. Patients with symptomatic cerebrovascular diseases, recent stroke or frequent transient ischaemic attacks have an increased risk of neurological complications.
In the case of severe renal insufficiency the coexistence of severe hepatic dysfunction can seriously delay contrast medium excretion, possibly necessitating haemodialysis.
Myeloma or paraproteinemia may predispose to renal impairment following contrast medium administration. Adequate hydration is mandatory.
Patients with phaeochromocytoma may develop a severe (occasionally uncontrollable) hypertensive crisis following intravascular contrast medium use. Premedication with alpha-receptor blockers is recommended.
Cases of severe vasculitis or Stevens-Johnson like syndrome have been reported in patients with pre-existing autoimmune disorders.
The administration of iodinated contrast media may aggravate the symptoms of myasthenia gravis.
Acute or chronic alcoholism may increase blood-brain barrier permeability. This facilitates the passage of the contrast medium into cerebral tissue, possibly leading to CNS reactions. Caution must also be exercised in alcoholics and drug addicts because of the possibility of a reduced seizure threshold.
Ionic iodinated contrast media inhibit blood coagulation, in vitro, more than non-ionic contrast media. Nevertheless medical personnel performing vascular catheterisation procedures should consider that numerous factors in addition to the contrast medium, including length of procedure, number of injections, catheter and syringe material, underlying disease state, and concomitant medication may contribute to the development of thromboembolic events. Therefore, when performing vascular catheterisation procedures one should be aware of this and pay meticulous attention to the angiographic technique and flush the catheter frequently with physiological saline (if possible with the addition of heparin) and minimize the length of the procedure so as to minimize the risk of procedure-related thrombosis and embolism.
The use of plastic syringes in place of glass syringes has been reported to decrease but not eliminate the likelihood of in vitro clotting.
Caution is advised in patients with homocystinuria because of the risk of inducing thrombosis and embolism.
The prevalence of delayed reactions (e.g. fever, rash, flu-like symptoms, joint pain and pruritus) to contrast media is higher in patients who have received interleukin.
Diabetic nephropathy may predispose to renal impairment following intravascular contrast medium administration. This may precipitate lactic acidosis in patients who are taking biguanides. As a precaution, biguanides should be stopped 48 hours prior to the contrast medium examination and reinstated only after adequate renal function has been regained.
Following the administration of iodinated contrast media, the capacity of the thyroid tissue to take up radioisotopes for diagnosing disorders of the thyroid is reduced for up to two weeks and even longer in individual cases.
It has not been sufficiently demonstrated that contrast media are safe for use in pregnant patients. Since, wherever possible, radiation exposure should be avoided during pregnancy, the benefits of any X-ray examination, with or without contrast media, should be carefully weighed against the possible risk.
Minimal amounts of salts of diatrizoic acid are excreted in human breast milk so harm to the breast-fed infant is not likely.
As with all iodinated contrast media, in rare cases there is a possibility of delayed reactions following contrast medium administration that could impair the ability to drive and use machines.
In order to give an approximate indication of incidence the following definitions apply when the words “common”, “uncommon” and “rare” appear in the text:
Side effects in association with the use of iodinated intravascular contrast media are usually mild to moderate and transient in nature. However, severe and life-threatening reactions as well as deaths have been reported. The prevalence of adverse drug reactions in patients receiving ionic contrast media is reported to be over 12% compared to 3% for nonionics. Nausea, vomiting, a sensation of pain and a general feeling of warmth are the most frequently recorded reactions.
Mild angioedema, conjunctivitis, coughing, pruritus, rhinitis, sneezing and urticaria have been reported commonly. These reactions, which can occur irrespective of the amount administered and the mode of administration, may be the first signs of incipient state of shock. Administration of the contrast medium must be discontinued immediately and – if necessary – specific therapy instituted via a venous access (see section 4.4, Special warnings and precautions for use).
Severe reactions requiring emergency treatment can occur in the form of a circulatory reaction accompanied by a peripheral vasodilatation and subsequent hypotension, reflex tachycardia, dyspnoea, agitation, confusion and cyanosis possibly leading to unconsciousness.
Hypotension, bronchospasm and laryngeal spasm or oedema occur uncommonly.
Delayed contrast medium reactions are rare (see section 4.4, Special warnings and precautions for use).
Heat sensations and headache have been reported as being common. Malaise, chills or sweating and vasovagal reactions are uncommon. In rare cases alterations in body temperature and swelling of salivary glands are possible.
Transient disturbance in respiratory rate, dyspnoea and respiratory distress and coughing are common.
Respiratory arrest and pulmonary oedema are rare reactions.
Clinically relevant transient disturbances in heart rate, blood pressure, disturbance in cardiac rhythm or function and cardiac arrest are uncommon.
Severe reactions requiring emergency treatment can occur in the form of a circulatory reaction accompanied by peripheral vasodilatation and subsequent hypotension, reflex tachycardia, dyspnoea, agitation, confusion and cyanosis possibly leading to unconsciousness.
Serious thromboembolic events causing myocardial infarction have been reported in rare cases.
Nausea and vomiting are common reactions. Abdominal pain has been reported as being uncommon.
Cerebral angiography and other procedures in which the contrast medium reaches the brain in high concentrations with the arterial blood can be accompanied by transient neurological complications such as: dizziness, headache, agitation or confusion, amnesia, disturbed speech, vision, hearing, convulsions, tremor, paresis/paralysis, photophobia, temporary blindness, coma and somnolence are uncommon.
Serious, in isolated cases fatal, thromboembolic events causing stroke have been reported on rare occasions.
In rare cases renal impairment or failures have been reported.
Mild angioedema, flush reaction with vasodilatation, urticaria, pruritus and erythema have been commonly observed. Toxic skin reactions such as the mucocutaneous syndrome (e.g. Stevens-Johnson’s or Lyell syndrome) may develop in rare cases.
Local pain occurs commonly, mainly in peripheral angiography. Extravasation of contrast media including Urografin gives rise to local pain and oedema but usually recedes without sequela. However, inflammation and even tissue necrosis have been seen on very rare occasions. Thrombophlebitis and venous thrombosis are uncommon.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance, Earlsfort Terrace, IRL – Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie.
In the absence of compatibility studies this medicinal product must not be mixed with other medicinal products.
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